碘催化的串联氧化环化反应合成多取代咪唑

以苯乙醛和苄胺衍生物为原料, 分子碘作为催化剂, 过氧叔丁醇作为氧化剂合成了一系列的多取代咪唑. 同时对反应过程中催化剂的用量、氧化剂、溶剂和温度进行了优化, 得到如下最优反应条件: 0.3 equiv.的分子碘作为催化剂, 过氧叔丁醇作为氧化剂, 乙腈作为溶剂, 反应温度为70℃. 而苯乙酮和苄胺上的吸电子基团均有利于此氧化反应, 对反应机理也进行了探索性研究并有了较明确的认识. 与传统的咪唑合成方法相比, 该新方法反应条件更温和, 原材料更易获得.     

Facile Access to Cyclopropylboronates via Stereospecific Deborylative Cyclization: A Leaving Group-Assisted Activation of Geminal Diborons

Herein we reported a transition metal-free deborylative cyclization strategy, based on which two routes have been developed, generating racemic and enantioenriched cyclopropylboronates. The cyclization of geminal-bis(boronates) bearing a leaving group was highly diastereoselective, tolerating a few functional groups and applicable to heterocycles. When optically active epoxides were used as the starting materials, enantioenriched cyclopropylboronates could be efficiently prepared with >99 % stereospecificity. Mechanistic studies showed that the leaving group at the γ-position played a crucial role and significantly promoted the activation of the gem-diboron moiety.     

Phototriggered Release of a Leaving Group in Ketoprofen Derivatives via a Benzylic Carbanion Pathway,But not via a Biradical Pathway

2‐Acetoxymethyl‐2‐(3‐benzoylphenyl)propionic acid (KP‐OAc) was used as a model to elucidate the solvent‐mediated photochemistry mechanism of Ketoprofen (KP). In solutions with a low concentration of water, KP‐OAc exhibits a benzophenone‐like photochemistry, reacting with water molecules through some reaction to form a ketyl radical intermediate. In neutral solutions with a high concentration of water or acidic solutions, KP‐OAc undergoes a photodecarboxylation reaction with the assistance of water molecules or with the catalysis of perchloric acid to directly generate a biradical intermediate that cannot induce the phototrigger reaction to release the AcO^? group. Therefore, the lifetime of the biradical intermediate of KP‐OAc is almost same as that of the biradical intermediate formed from KP in the same kinds of solutions. However, the photodecarboxylation of KP‐OAc in phosphate buffer solution directly produces the benzylic carbanion intermediate, which can induce the phototrigger reaction to release the AcO^? group. Therefore, the lifetime of the biradical intermediate of KP‐OAc is significantly shorter than the lifetime of the biradical intermediate of KP in phosphate buffer solution. Interestingly, the investigation of the photochemistry of KP‐OAc not only verifies the solvent‐mediated photochemistry mechanism of KP but also provides some new insight into the potential of using this kind of platform for phototrigger applications. The biradical intermediate is not the key species leading to the phototrigger reaction but the benzylic carbanion species is the key reactive intermediate that can mediate the phototrigger reaction of KP‐OAc. Therefore, a change in the pH of the solutions can be utilized to switch on and switch off the photorelease reactions of KP derivative phototrigger compounds.     

Remote Electronic Tuning of Chiral N-Heterocyclic Carbenes

Our recent efforts to develop novel N-Heterocyclic carbene (NHC)-catalyzed asymmetric reactions are described. During our investigation for development of the acylation reactions via acylazoliums generated by the reactions of NHCs and α-oxidized aldehydes, we have observed significant effects of substitution at a remote site of the carbene carbon of NHCs. In addition, we also observed a significant enhancement of the enantioselectivity by the addition of carboxylate anions. From this observation, we proposed a novel working hypothesis involving a formation of a complex of the substrate and additive to reinforce the recognition of the catalyst for enhancement of the catalytic performance of the asymmetric N-heterocyclic carbene system. By applying this concept, we achieved the kinetic resolutions of both cyclic and acyclic alcohols in excellent enantioselectivities. The effects of the remote substitution were also observed in intramolecular Stetter reaction and intermolecular benzoin reaction. In these reactions, the comparison of the catalytic performance of the NHCs bearing variable remote substitutions provided insights into the reaction mechanism because the remote substitution tuned the electronic nature of NHCs without affecting the steric and electrostatic factors around the reaction site. We also developed an intramolecular benzoin condensation involving two aldehydes, which is challenging to realize. Using the substrates bearing proper protecting groups, we succeeded in the stereo divergent synthesis of a variety of inososes, which are important intermediates for the synthesis of biologically active cyclitols.     

Synthetic Applications of Carbonyl Ylides Generated via the Tandem Cyclization Cycloaddition Reaction of Rhodium Carbenoids

The author's chemical studies dealing with the generation of carbonyl ylides via the rhodium(II) induced cyclization of α-diazo alkanediones are summarized, Dipole formation occurs by reaction of a transient rhodium carbenoid intermediate with a neighboring carbonyl group. These cyclizations are performed under extremely mild conditions, typically at room temperature in a neutral organic solvent. Since these cycloadditions involve carbonyl ylides, the resulting products are oxabicycles of varying ring size. When the dipolarophile is intramolecularly tethered to the dipole, the subsequent cycloaddition affords complex oxapolycyclic systems with three (or more) component rings.     

Silver-Catalyzed Tandem Cyclization for Syntheses of Azaoxa- and Diazaspirocycles**

1-Azaspirocycles are important structures present in many drugs and natural products. This work describes the silver-catalyzed tandem cyclization strategy, which provides atom-economical access to various azaoxa- and diazaspirocycles from alkynes containing two appended oxygen- and nitrogen-based nucleophiles. Intramolecular attack of the pendant nucleophile on the in situ-generated iminium intermediate is the key to the success of this transformation.     

有机催化不对称Michael/环化串联反应的研究进展北大核心CSCD

串联反应能够减少反应步骤、简化操作、降低成本、实现高效率转化,符合原子经济性和绿色化学理念.特别是有机催化的不对称串联环化反应以一锅法连续催化多个化学反应,为高效合成多手性中心环状结构提供了新方法.不对称Michael/环化串联反应是构建光学活性状化合物的常用方法之一,近些年,各种有机小分子催化剂应用于不对称Michael/环化串联反应的报道不断增加,并且取得了重大进展.我们根据不同的催化剂类型综述了近5年来关于不对称Michael/环化串联反应的研究进展,并对有机催化不对称Michael/环化串联反应的发展趋势进行了展望.     

邻-酚羟基取代N-杂环卡宾[C,O]螯合双配体镍/MAO催化降冰片烯加成聚合的研究

3种邻-酚羟基取代的N-杂环卡宾[C,O]螯合双配体镍配合物在甲苯中以甲基铝氧烷(MAO)为助催化剂,催化降冰片烯(NBE)聚合.考察了反应温度、时间、n(Al)/n(Ni)以及n(NBE)/n(Ni)等因素对催化活性和所得聚降冰片烯相对分子质量及其分布的影响.结果表明,0℃时催化体系的聚合活性可达,1.34×107gPNBE/(molNi.h);所得聚降冰片烯(PNBE)重均相对分子质量(Mw)可达2.0×106,相对分子质量分布(Mw/Mn)为3.3~1.5,热分解温度在440℃附近,且在室温下可溶于环己烷和三氯苯.通过对聚合产物FTIR,13C-NMR和WAXD分析表明,该聚合反应以烯烃加成聚合方式进行,且聚合物是非晶态结构.     

One‐Pot Green Synthesis of Thiazolo[3,2‐a]pyridine Derivatives via Tandem Cyclization in Aqueous Media

Facile, three‐component domino reactions of readily available thioglycolic acid/ethyl thioglycolate, aromatic aldehydes, and malononitrile/ethyl cyanoacetate in aqueous potassium carbonate at room temperature afforded thiazolo[3,2‐a]pyridine derivatives chemoselectively in good to excellent yield. All the formed 4H‐chromenes were characterized by spectral and X‐ray methods.     

Synthesis of an Azasteroid Using an Acyl Iminium Ion-Initiated Tandem Cyclization

An acyl iminium ion-initiated tandem cyclization gave an unexpected dienone product, a seco-azasteroid (2). The factors governing the formation of 2 were investigated in an attempt to optimize its formation. The reaction was applied to a more elaborate system, resulting in the synthesis of the full steroid skeleton of 13-azaandrosta-1,4-diene-3,17-dione (3), which contains the unusual substitution of a chlorine atom for the axial 19-methyl.     

Mechanism and Origins of Diastereo- and Regioselectivities of Palladium-Catalyzed Remote Diborylative Cyclization of Dienes via Chain-Walking Strategy

Density functional theory calculations have been performed to investigate the palladium-catalyzed remote diborylative cyclization of dienes. The computations reveal that the reaction proceeds through a rarely explored Pd(II)/Pd(IV) catalytic cycle, and the formal σ-bond metathesis between the alkylpalladium intermediate and B₂pin₂ occurs via the pathway of the B−B oxidative addition/C−B reductive elimination involving the high-valent Pd(IV) species. The diastereoselectivity is determined by the migratory insertion into the Pd−C bond, which is mainly due to the combination of the torsional strain effect, steric repulsion and C−H—O hydrogen-bonding interaction. The steric hindrance around the reacting carbon group in the C−B reductive elimination turns out to be a key factor to provide the driving force of the chain walking of the Pd center to the terminal primary carbon position, enabling the experimentally observed remote regioselectivity.     

Cyclization via carbolithiation of alpha-amino alkyllithium reagents

We report a new route to tertiary alpha-amino stereocenters by sequential alkylation of alpha-amino nitriles followed by reductive lithiation of the nitrile and cyclization onto an alkene. Reductive lithiation of alpha-amino nitriles using lithium 4,4'-di-tert-butylbiphenylide (LiDBB) and subsequent intramolecular carbolithiation proceeded with modest to high diastereoselectivity to deliver cyclic or spirocyclic ring systems. The stereoselectivity of these intramolecular carbolithiations was examined using density function calculations to evaluate plausible transition state models.     

Tandem Sulfonylation/Cyclization of Vinyl Azides with Aryldiazonium Tetrafluoroborates and SO2

An efficient and facile strategy for the synthesis of 6-(sulfonylmethyl)phenanthridines and its derivatives has been developed via tandem sulfonylation cyclization of vinyl azides under mild conditions in the absence of any catalysts and additives. The reaction simply utilizes easily accessible and cheap K₂S₂O₅ as the sulfur dioxide source, delivering functionalized phenanthridines in moderate to excellent yields with operational simplicity and gram-scale synthesis, as well as good functional-group tolerance.     

Palladium-Catalyzed Tandem Carbonylative Aza-Wacker-Type Cyclization of Nucleophile Tethered Alkene to Access Fused N-Heterocycles

Although tandem reactions offer rapid access to structurally complex molecules in one-pot reaction,the selectivity issue needs to be addressed particularly when incompatible step reactions are involved.Herein,we report the selective synthesis of fused N-heterocycles from nucleophile-tethered alkenylamide and carbon monoxide via palladium(Pd)-catalyzed tandem carbonylative aza-Wacker-type cyclization.The electron-deficient nature of amide N—H and the intramolecular coordination of Pd with alkene accelerate the aminopalladation and effectively prevent the side oxidative carbonylation of diamine moiety to form urea.It is also found that the reported acyl Pd chloride intermediate may not be involved in this tandem cyclization.This work not only provides an efficient synthetic route to fused 1,4-diazepanones and 1,4-diazepanes but also inspires further development of tandem reactions for the diverse synthesis of heterocycles.